Below are the results of the systematic review and meta-analysis
including a PRISMA flow diagram (Page et al 2021) for details of the
flow of study selection, a table of characteristics for included
studies, risk of bias assessment, forest plots for each outcome with
accompanying descriptive text.
Description of included studies
We identified 61 eligible studies. The study characteristics can be
found in Table 1. Data from studies contributed with at
least one outcome with quantitative data (total of 9745 participants),
which included adults from multiple countries. The mean age of
participants was 42.4 years (range 15 to 72 years), with a mean
proportion of 0.58 female participants (range 0 to 0.86). Included
studies allocated the participants to treatment lasting between 4 to
12.9 weeks (median, 6 weeks).
Primary outcome: reduction in anhedonia scores at 8 weeks (from 4 to
12 weeks)

Figure X Forest plot for symptoms of anhedonia
(primary outcome) comparing pro-dopaminergic interventions vs placebo
for individuals with anhedonia at 4-12 weeks (primary timepoint). SMD:
standardised mean difference, 95%CI: 95% confidence intervals, SD:
standard deviation.
6 studies contributed with data to the meta-analysis with a total of
2079 participants (1143 allocated to pro-dopaminergic interventions, 936
allocated to pill placebo).
The comparative effect of pro-dopaminergic interventions versus
placebo showed an effect favouring pro-dopaminergic interventions with a
SMD of -0.244 (95%CI from -0.456 to -0.032). The study results presented
an I2 value of 67.8% (95%CI from 23.6% to 86.4%) and a tau2 value of
0.025 (accounting for a 95% prediction interval from -0.74 to
0.252).
Risk of bias
Sensitivity analyses
Secondary outcome: Reduction in mean anxiety score at 8 weeks (from
4 to 12 weeks)

Figure X Forest plot for symptoms of anxiety
(secondary outcome) comparing pro-dopaminergic interventions vs placebo
for individuals with anxiety at 4-12 weeks (primary timepoint). SMD:
standardised mean difference, 95%CI: 95% confidence intervals, SD:
standard deviation.
11 studies contributed with data to the meta-analysis with a total of
3517 participants (2077 allocated to pro-dopaminergic interventions,
1440 allocated to pill placebo.
The comparative effect of pro-dopaminergic interventions versus
placebo showed an effect favouring pro-dopaminergic interventions with a
SMD of -0.166 (95%CI from -0.243 to -0.088). The study results presented
an I2 value of 0% (95%CI from 0% to 60.2%) and a tau2 value of 0
(accounting for a 95% prediction interval from -0.251 to -0.08).
Secondary outcome: Dropouts due to any reason

Figure X Forest plot for dropouts due to any reason
for the comparison of pro-dopaminergic interventions vs placebo at 4-12
weeks. OR: odds ratio, 95%CI: 95% confidence intervals.
50 studies contributed with data to the meta-analysis with a total of
0 participants ( allocated to pro-dopaminergic interventions, allocated
to pill placebo).
The comparative effect of pro-dopaminergic interventions versus
placebo showed an effect favouring pro-dopaminergic interventions with a
SMD of -0.092 (95%CI from -0.315 to 0.13). The study results presented
an I2 value of 67.6% (95%CI from 56.6% to 75.8%) and a tau2 value of
0.334 (accounting for a 95% prediction interval from -1.274 to
1.089).
Secondary outcome: dropouts due to side effects

Figure X Forest plot for dropouts due to adverse
events for the comparison of pro-dopaminergic interventions vs placebo
at 4-12 weeks. OR: odds ratio, 95%CI: 95% confidence intervals.
40 studies contributed with data to the meta-analysis with a total of
0 participants ( allocated to pro-dopaminergic interventions, allocated
to pill placebo).
The comparative effect of pro-dopaminergic interventions versus
placebo showed an effect favouring pro-dopaminergic interventions with a
SMD of 0.552 (95%CI from 0.227 to 0.876). The study results presented an
I2 value of 45.7% (95%CI from 21.1% to 62.6%) and a tau2 value of 0.395
(accounting for a 95% prediction interval from -1.274 to 1.863).
Meta-regressions were conducted for age, sex, and baseline anxiety
score. Of these, only sex was a significant predictor of dropouts due to
adverse events with a beta=-2.960, SE=1.21 95%CI (-5.423; -0.497) and an
R^2=40.63% and p=.022.
Secondary outcome: nausea

Figure X Forest plot for nausea for the comparison
of pro-dopaminergic interventions vs placebo at 4-12 weeks. OR: odds
ratio, 95%CI: 95% confidence intervals.
24 studies contributed with data to the meta-analysis with a total of
0 participants ( allocated to pro-dopaminergic interventions, allocated
to pill placebo).
The comparative effect of pro-dopaminergic interventions versus
placebo showed an effect favouring pro-dopaminergic interventions with a
SMD of 0.378 (95%CI from 0.169 to 0.586). The study results presented an
I2 value of 27.4% (95%CI from 0% to 56%) and a tau2 value of 0.065
(accounting for a 95% prediction interval from -0.19 to 0.945).
Secondary outcome: headache

Figure X Forest plot for headaches for the
comparison of pro-dopaminergic interventions vs placebo at 4-12 weeks.
OR: odds ratio, 95%CI: 95% confidence intervals.
26 studies contributed with data to the meta-analysis with a total of
0 participants ( allocated to pro-dopaminergic interventions, allocated
to pill placebo).
The comparative effect of pro-dopaminergic interventions versus
placebo showed an effect favouring pro-dopaminergic interventions with a
SMD of 0.149 (95%CI from 0.029 to 0.269). The study results presented an
I2 value of 0% (95%CI from 0% to 43.2%) and a tau2 value of 0
(accounting for a 95% prediction interval from 0.008 to 0.291).
Secondary outcome: insomnia

Figure X Forest plot for insomnia for the comparison
of pro-dopaminergic interventions vs placebo at 4-12 weeks. OR: odds
ratio, 95%CI: 95% confidence intervals.
22 studies contributed with data to the meta-analysis with a total of
0 participants ( allocated to pro-dopaminergic interventions, allocated
to pill placebo).
The comparative effect of pro-dopaminergic interventions versus
placebo showed an effect favouring pro-dopaminergic interventions with a
SMD of 0.583 (95%CI from 0.354 to 0.812). The study results presented an
I2 value of 5.4% (95%CI from 0% to 37.7%) and a tau2 value of 0.03
(accounting for a 95% prediction interval from 0.15 to 1.017).
Secondary outcome: constipation

Figure X Forest plot for dropouts due to adverse
events for the comparison of pro-dopaminergic interventions vs placebo
at 8 (4-12) weeks. OR: odds ratio, 95%CI: 95% confidence intervals.
19 studies contributed with data to the meta-analysis with a total of
0 participants ( allocated to pro-dopaminergic interventions, allocated
to pill placebo).
The comparative effect of pro-dopaminergic interventions versus
placebo showed an effect favouring pro-dopaminergic interventions with a
SMD of 0.439 (95%CI from 0.222 to 0.656). The study results presented an
I2 value of 0% (95%CI from 0% to 48.9%) and a tau2 value of 0
(accounting for a 95% prediction interval from 0.183 to 0.696).
There were no significant subgroup differences between participants
assigned to different classes of drug.
Secondary outcome: dizziness

Figure X Forest plot for dizziness for the
comparison of pro-dopaminergic interventions vs placebo at 8 (4-12)
weeks. OR: odds ratio, 95%CI: 95% confidence intervals.
22 studies contributed with data to the meta-analysis with a total of
0 participants ( allocated to pro-dopaminergic interventions, allocated
to pill placebo).
The comparative effect of pro-dopaminergic interventions versus
placebo showed an effect favouring pro-dopaminergic interventions with a
SMD of 0.543 (95%CI from 0.28 to 0.805). The study results presented an
I2 value of 26.5% (95%CI from 0% to 56.4%) and a tau2 value of 0.084
(accounting for a 95% prediction interval from -0.115 to 1.2).
Secondary outcome: dry mouth

Figure X Forest plot for dry mouth for the
comparison of pro-dopaminergic interventions vs placebo at 4-12 weeks.
OR: odds ratio, 95%CI: 95% confidence intervals.
24 studies contributed with data to the meta-analysis with a total of
0 participants ( allocated to pro-dopaminergic interventions, allocated
to pill placebo).
The comparative effect of pro-dopaminergic interventions versus
placebo showed an effect favouring pro-dopaminergic interventions with a
SMD of 0.751 (95%CI from 0.519 to 0.983). The study results presented an
I2 value of 36.1% (95%CI from 0% to 61%) and a tau2 value of 0.08
(accounting for a 95% prediction interval from 0.126 to 1.376).
Secondary outcome: vomiting

Figure X Forest plot for vomiting for the comparison
of pro-dopaminergic interventions vs placebo at 4-12 weeks. OR: odds
ratio, 95%CI: 95% confidence intervals.
5 studies contributed with data to the meta-analysis with a total of
0 participants ( allocated to pro-dopaminergic interventions, allocated
to pill placebo).
The comparative effect of pro-dopaminergic interventions versus
placebo showed a comparable effect not excluding the null effect with a
SMD of 0.641 (95%CI from -0.104 to 1.386). The study results presented
an I2 value of 2.2% (95%CI from 0% to 79.7%) and a tau2 value of 0
(accounting for a 95% prediction interval from -0.204 to 1.485).